title: Etravirine-based highly active antiretroviral therapy in HIV-1-infected paediatric patients.
abstract: BACKGROUND
  We evaluated the efficacy, safety and tolerability of etravirine in paediatric patients vertically infected with HIV-1.
  
  
  METHODS
  A multicentre retrospective study of 23 multidrug-resistant paediatric patients (five children and 18 adolescents) enrolled in the study from 1 September 2007 to 28 February 2010 was carried out. We performed a longitudinal analysis of immunological, virological and clinical data.
  
  
  RESULTS
  The median age of the patients was 14.2 years [interquartile range (IQR) 12.5-15.8 years]. At baseline, the median HIV-1 RNA was 29 000 (4.5 log(10) ) HIV-1 RNA copies/mL (range 4300-83 000 copies/mL), the median CD4 T-cell count was 445 cells/μL (range 221-655 cells/μL) and the median CD4 percentage was 19.6% (IQR 13.0-31.0). Remarkably, 16 of 23 patients (70%) harboured one or more etravirine-associated resistance mutations. The backbone regimen included at least two fully active drugs in 91% of patients. After etravirine-based therapy, 20 patients (87%) achieved HIV-1 RNA<400 copies/mL and 18 of 23 (78%) achieved HIV-1 RNA<50 copies/mL: three (13%) within the first month, seven (30%) within the first 4 months, and six (26%) between the 5th and 8th months. CD4 T-cell recovery was observed in 19 patients (83%). The median follow-up time was 48.4 weeks (IQR 35.7-63.4 weeks); four patients (17%) were exposed to etravirine for >120 weeks. Three mild/short-term and two moderate skin rashes were observed in the adolescents. Laboratory abnormalities included hypercholesterolaemia (11 of 23 patients), hypertriglyceridaemia (eight of 23 patients), and reduced high-density lipoprotein cholesterol (10 of 23 patients). Adherence was complete in seven patients (30%). No patients showed complete resistance to etravirine after follow-up. However, three of 21 patients (14%) who initially showed intermediate resistance interrupted etravirine treatment because of virological failure.
  
  
  CONCLUSIONS
  We observed a sustained antiviral response and improved immunological parameters in multidrug-resistant paediatric patients, most of whom had received etravirine as part of salvage regimens with at least two fully active drugs.
authors.affiliation: Laboratory of Immunomolecular Biology, Hospital General Universitario 'Gregorio Marañón', Madrid, Spain.
authors.forename: V
authors.initials: V
authors.lastname: Briz
authors.forename: C
authors.initials: C
authors.lastname: Palladino
authors.forename: Ml
authors.initials: M
authors.lastname: Navarro
authors.forename: S
authors.initials: S
authors.lastname: Jiménez de Ory
authors.forename: Mi
authors.initials: M
authors.lastname: González-Tomé
authors.forename: Ja
authors.initials: J
authors.lastname: León
authors.forename: E
authors.initials: E
authors.lastname: Núñez-Cuadros
authors.forename: Mi
authors.initials: M
authors.lastname: de José
authors.forename: Jt
authors.initials: J
authors.lastname: Ramos
authors.forename: Ma
authors.initials: M
authors.lastname: Muñoz-Fernández
mesh_terms: D000293:Adolescent; D023241:Antiretroviral Therapy, Highly Active; D018791:CD4 Lymphocyte Count; D002648:Child; D002675:Child, Preschool; D024882:Drug Resistance, Viral; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000453:epidemiology; D015497:HIV-1 / Q000187:drug effects*; D006801:Humans; D008297:Male; D009570:Nitriles; D011724:Pyridazines / Q000627:therapeutic use*; D011743:Pyrimidines; D012189:Retrospective Studies; D013030:Spain / Q000453:epidemiology; D016896:Treatment Outcome
chemical_list: D009570:Nitriles; D011724:Pyridazines; D011743:Pyrimidines; C451734:etravirine